DESCRIPTION: Indole-3-carbinol (I3C) is a naturally occurring component of cruciferous vegetables and has promise as a cancer preventive agent, most notably against breast cancer. The hypothesis to be tested in this proposal is that the antiestrogenic growth inhibitory activity of I3C results from its conversion to products which bind to the aryl hydroxylase receptor (AhR) leading to increased estrogen metabolism and/or decreased cell sensitivity to estrogen. Three specific aims are proposed to investigate this hypothesis: (1) identify I3C products that are responsible for I3C's growth inhibitory effects in estrogen-responsive tumor cells; (2) determine AhR-related activities of growth inhibitors; and (3) characterize antiestrogenic effects of growth inhibitors and determine whether the AhR is required for these effects. In order to carry out this work, the investigators propose to fractionate reaction mixtures resulting from acid or neutral treatment of I3C and examine the purified conversion products for growth inhibitory activity using estrogen responsive MCF-7 cells. Growth inhibitory products will then be further analyzed for their effects on AhR and estrogen receptor mediated gene expression, receptor affinity, receptor binding to response elements, and induction of AhR and ER-responsive reporter constructs in transfected tumor cells. To determine if the growth inhibitory effects of the I3C conversion products depend on AhR, AhR antisense blocking experiments will be conducted.